The present invention relates to the murine monoclonal antibody (mAb) 11B9 and to mAb 62 each of which target major neutralizing epitopes of influenza A H7 hemagglutinin and active fragments thereof. The present invention also relates to methods and compositions for the prophylaxis and treatment of H7 influenza using murine mAb 11B9, mAb 62 or fragments thereof. The present invention further relates to methods and kits for determining, identifying and/or quantifying (a) influenza A hemagglutinin in a sample or vaccine or (b) an antibody against influenza A hemagglutinin.
The publications and other materials used herein to illuminate the background of the invention or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the Bibliography.
Occurrence of highly pathogenic avian influenza (HPAI) subtype H7 in poultry continues to be a public health concern (Jadhao et al., 2008; Abbas et al., 2011). Influenza A H7 subtype viruses from both Eurasian and North American lineages have resulted in more than 100 cases of human infection since 2002 in the Netherlands, Italy, Canada, the United Kingdom, and the United States. In 2003, an HPAI H7N7 outbreak in the Netherlands infected 89 people in close contact with affected poultry and resulted in one fatal case. These cases include outbreaks of HPAI H7N7 virus in the Netherlands in 2003 that resulted in more than 80 cases of human infection and one fatality; HPAI H7N3 virus in British Columbia, Canada, in 2004 that resulted in two cases of conjunctivitis; a cluster of human infections of low-pathogenicity avian influenza (LPAI) H7N2 virus in the United Kingdom in 2007 that resulted in several cases of influenza-like illness and conjunctivitis; and a single case of respiratory infection in New York in 2003. H7 subtype viruses have presented significant pandemic potential (Min et al., 2010).
Humans are immunologically naïve to the H7 avian influenza viruses, and LPAI H7 subtype viruses circulating in domestic poultry and wild birds in Eurasia and North America have the potential to evolve and acquire an highly pathogenic phenotype either by accumulating mutations or by recombination at the hemagglutinin (HA) cleavage site resulting in a highly cleavable HA that is a virulence motif in poultry. Recent work also suggests that contemporary North American lineage H7 subtype viruses, isolated in 2002 to 2003, are partially adapted to recognize 2-6-linked sialic acids, which are the receptors preferred by human influenza viruses and are preferentially found in the human upper respiratory tract (Gambaryan et al., 2012). Moreover, coinfection and genetic reassortment of RNA genomes between H7 avian influenza viruses and human influenza viruses, including the seasonal H1N1 and H3N2 and pandemic H1N1 viruses, could result in the generation of reassortant viruses with the capacity to efficiently transmit among people and result in a pandemic. Domesticated birds may serve as important intermediate hosts for the transmission of wild-bird influenza viruses to humans, as may pigs, as evidenced by human infections with swine-origin 2009 pandemic H1N1 influenza virus throughout the world.
Passive immunotherapy using monoclonal antibodies has been viewed as a viable option for treatment of many infectious diseases. Currently, there has been a lot of focus on therapeutic approaches using neutralizing antibodies against the HA1 protein of the influenza virus (Prabakaran et al., 2009). This protein is easy to target as it is on the surface of the virus and antibodies against this protein can neutralize the virus efficiently. Hence, monoclonal antibodies against neutralizing epitopes of H7 hemagglutinin (HA) may be an attractive alternative to active vaccination of humans, in particular for those individuals who are at high risk from influenza infection, such as the immuno-compromised patients or the elderly who do not respond well to active immunization. It is important that any mAb product should offer broad protection against circulating strains of H7 influenza.
It is desired to identify monoclonal antibodies that can be used for the prophylaxis and treatment of H7 influenza.